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For those LSDs, postnatal enzyme replacement therapy (ERT) represents the standard of care, but this treatment has limitations when administered only postnatally because, at that point, prenatal disease sequelae may be irreversible. Furthermore, most forms of ERT, specifically those administered systemically, are currently unable to access certain tissues, such as the central nervous system (CNS), and furthermore, may initiate an immune response. In utero enzyme replacement therapy (IUERT) is a novel approach to address these challenges evaluated in a first\u2010in\u2010human clinical trial for IUERT in LSDs (NCT04532047). IUERT has numerous advantages: in\u2010utero intervention may\u00a0prevent early pathology; the CNS can be accessed before the blood\u2010brain barrier forms; and the unique fetal immune system enables exposure to new proteins with the potential to prevent an immune response and may induce sustained tolerance. However, there are challenges and limitations for any fetal procedure that involves two patients. This article reviews the current state of IUERT for LSDs, including its advantages, limitations, and potential future directions for definitive therapies.<\/jats:p>","DOI":"10.1002\/pd.6460","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T15:00:09Z","timestamp":1699887609000},"page":"1638-1649","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Intrauterine enzyme replacement therapies for lysosomal storage disorders: Current developments and promising future prospects"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-4099","authenticated-orcid":false,"given":"Akos","family":"Herzeg","sequence":"first","affiliation":[{"name":"Center for Maternal\u2010Fetal Precision Medicine University of California  San Francisco California USA"},{"name":"Department of Surgery University of California  San Francisco California 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